LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model
Background. LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardia...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Cardiovascular Therapeutics |
| Online Access: | http://dx.doi.org/10.1155/2019/6032631 |
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| author | Po-Cheng Chang Shien-Fong Lin Yen Chu Hung-Ta Wo Hui-Ling Lee Yu-Chang Huang Ming-Shien Wen Chung-Chuan Chou |
| author_facet | Po-Cheng Chang Shien-Fong Lin Yen Chu Hung-Ta Wo Hui-Ling Lee Yu-Chang Huang Ming-Shien Wen Chung-Chuan Chou |
| author_sort | Po-Cheng Chang |
| collection | DOAJ |
| description | Background. LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear. Methods. We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week after MI to confirm the development of HF with left ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. The sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins. Results. The HF-vehicle group did not show significant changes in LVEF. Both enalapril and LCZ696 therapy significantly improved LVEF. The HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy significantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed significant downregulation of NaV1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2. Conclusion. As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K+ channel proteins. |
| format | Article |
| id | doaj-art-b6649915a4194b7fb3a330979bd61e73 |
| institution | Kabale University |
| issn | 1755-5914 1755-5922 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cardiovascular Therapeutics |
| spelling | doaj-art-b6649915a4194b7fb3a330979bd61e732025-02-03T01:28:40ZengWileyCardiovascular Therapeutics1755-59141755-59222019-01-01201910.1155/2019/60326316032631LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat ModelPo-Cheng Chang0Shien-Fong Lin1Yen Chu2Hung-Ta Wo3Hui-Ling Lee4Yu-Chang Huang5Ming-Shien Wen6Chung-Chuan Chou7Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, TaiwanInstitute of Biomedical Engineering, National Chiao Tung University, Hsinchu, TaiwanChang Gung University College of Medicine, TaiwanDivision of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, TaiwanDepartment of Anesthesia, Chang Gung Memorial Hospital, Taipei, TaiwanDivision of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, TaiwanDivision of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, TaiwanDivision of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, TaiwanBackground. LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear. Methods. We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week after MI to confirm the development of HF with left ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. The sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins. Results. The HF-vehicle group did not show significant changes in LVEF. Both enalapril and LCZ696 therapy significantly improved LVEF. The HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy significantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed significant downregulation of NaV1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2. Conclusion. As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K+ channel proteins.http://dx.doi.org/10.1155/2019/6032631 |
| spellingShingle | Po-Cheng Chang Shien-Fong Lin Yen Chu Hung-Ta Wo Hui-Ling Lee Yu-Chang Huang Ming-Shien Wen Chung-Chuan Chou LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model Cardiovascular Therapeutics |
| title | LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model |
| title_full | LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model |
| title_fullStr | LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model |
| title_full_unstemmed | LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model |
| title_short | LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model |
| title_sort | lcz696 therapy reduces ventricular tachyarrhythmia inducibility in a myocardial infarction induced heart failure rat model |
| url | http://dx.doi.org/10.1155/2019/6032631 |
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